This is an application for the renewal for the Rat Genome EST Project (RGP/EST). The rat model and the continuation of this project is important for several reasons. First, a direct result of RHP/EST is the identification of a large number of novel genes (U. of Iowa). Second, large numbers of quantitative traits have been and are being mapped in various rat models. Third, the rat remains a major model for biomedical research within both academia and industry, with a long history of physiological and biochemical studies. Fourth, rat ESTs with identifiable human and/or mouse homologs provide integration points for comparative mapping, which enables investigators to "walk" between species and link the physiology of the rat with the genetics of the mouse and the clinical relevance in the human. As outlined in the progress report, tremendous strides have been made in the RGP/EST. Fifth, RGP/EST will help to accelerate the discovery of genes and pathways involved in common disease by enabling investigators who have mapped quantitative trait loci (QTLs) to identify positional candidate genes within the intervals directly or through additional links to the human sequence via comparative mapping. The investigators have joined forces with the U. of Iowa group to use the combined existing infrastructure to map 27,000 additional rat ESTs (15,000 MCW + 12,000 U. of Iowa). The division of labor is designed to keep both RH mapping teams intact without markedly expanding equipment or numbers of personnel. While this relationship is formalized in these renewal applications, the two groups have coordinated efforts and worked together from the start. MCW has initiated the development of a "backbone" map to provide the means to integrate genetic maps, to facilitate comparative mapping, and to initiate the framework for the physical map. This backbone, built on both genetic markers and genes/ESTs, requires three components: mapping large numbers of genetic markers (largely completed) and genes ESTs, constructing the comparative maps and finally virtual mapping. They will map an additional 15,000 ESTs with sequence homology to human and mouse genes/ESTs that have been mapped. The combined efforts (MCW and U. of Iowa) will result in more than 1/3 of all rat genes mapped and placed on the RH "backbone" map facilitating comparative genomics with sequence "hooks".